TMEM-MRI: A Pilot Feasibility Study of MRI for Imaging of TMEM in Patients With Operable Breast Cancer (TMEM-MRI)

TMEM-MRI: A Pilot Feasibility Study of Magnetic Resonance Imaging for Imaging of TMEM (Tumor Microenvironment of Metastasis) in Patients With Operable Breast Cancer

The aim of this study is to assess feasibility of a new imaging technology in the management of breast cancer (TMEM-MRI)

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer
• Intervention / Treatment: Device: TMEM-MRI; Procedure: FNA

Detailed Description

The goal of this study is to assess the feasibility of a new imaging technology in the management of breast cancer. Tumor Microenvironment of Metastasis - Magnetic Resonance imaging (TMEM-MRI) has the ability to detect tumor areas with more leakiness (perfusion), where cancer cell enter blood vessels to travel to other sites. This novel TMEM-MRI has potential to be used in clinical practice to identify tumors with high leakiness that might have higher chances to recur after breast cancer treatment. In addition, TMEM-MRI can potentially be used to assess response to preoperative treatments (chemotherapy, hormonal therapy) over time.

• Study Type: Interventional
• Enrollment (Estimated): 75
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jesus Anampa, MD,MS; Phone Number: 7184058505; Email: janampa@montefiore.org

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Recruiting
      • Montefiore Medical Center
      • Principal Investigator: Jesus Anampa, MD
      • Contact: Jesus D Anampa, MD,MS; Phone Number: 718-405-8505; Email: janampa@montefiore.org
      • Sub-Investigator: Joseph Sparano, MD
      • Contact: Karen Fehn, RN; Phone Number: 7184058505; Email: kfehn@montefiore.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria

• For pre-pilot phase (MRI sequence development):

  o Patients with a breast mass, with biopsy-proven histology of invasive breast carcinoma (any histologic type and ER,PR,HER2 status)

• For pilot phase cohort A:

  o Patients with a breast mass considered highly suspicious for invasive carcinoma by the radiologist (BIRADS 5).

• For pilot phase cohort B:

  • Patients with a breast mass found to be invasive ductal carcinoma on core biopsy.
  • The tumor should be considered operable by the breast surgeon.
  • No preoperative therapy for the current breast cancer is planned (endocrine therapy, chemotherapy, or radiation).
• Tumor size/breast mass should be > 1 cm in largest diameter (radiologically).
• Multifocal disease is allowed, as long as patients meet all eligibility criteria.
• Age ≥ 18 years.
• ECOG performance status 0-1.
• Willingness to undergo a "research breast MRI".

• Patient must be able to undergo MRI with gadolinium enhancement.

  • No history of untreatable claustrophobia.
  • No presence of non MRI compatible metallic objects or metallic objects that, in the opinion of a radiologist, would make MRI a contraindication.
  • No history of sickle cell disease.
  • No contraindication to intravenous contrast administration.
  • No known allergy-like reaction to gadolinium
  • No known or suspected renal impairment. GFR should be greater than 30 mL/min/1.73 m2.
• Weight less than or equal to the MRI table limit.
• Ability to understand and willingness to sign a written informed consent.

Exclusion Criteria

• Patients may not have had breast cancer or radiation therapy to the ipsilateral breast in the past.
• No breast prosthetic implants (silicone or saline) are allowed.
• Use of any investigational agent within 30 days of starting study.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study.
• Patients must be non-pregnant and non-lactating. Patients must have a negative pregnancy test (urine or serum) within 7 days of registration date.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Pre-biopsy patients; Patients identified by a radiologist at the time of diagnostic evaluation. Once consent is obtained, the TMEM-MRI will be scheduled. After TMEM-MRI, the patient will undergo core biopsy as per usual radiology procedure, with additional FNA at the time of core biopsy (preceding the core biopsy). MenaINV and MenaCalc will be calculated from the FNA material. After the breast biopsy confirms the suspected diagnosis of invasive breast carcinoma, the patient will be referred to breast surgery and a treatment plan devised, as per NCCN/ASCO guidelines. TMEM density, MenaCalc and MenaINV will be also calculated from the specimen obtained at the time of definitive surgery. Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV.	Device: TMEM-MRI; TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.; Procedure: FNA; FNA: The patients who are recruited prior to biopsy (Cohort A) will have had TMEM-MRI performed prior to biopsy. They will then present to radiology for ultrasound-guided core biopsy of the breast mass. FNA will be performed during this procedure. The FNA will be performed after local anesthetic is administered but prior to insertion of the core biopsy needle. FNA will be performed by the radiologist under direct sonographic visualization of the mass. Five passes will be obtained with a 25 gauge needle. The FNA material will be expelled into 1.5 ml Eppendorf tube containing phosphate buffered saline with EDTA.
Other: Post-biopsy patients; Patients after breast biopsy. Once consent is obtained, patients will undergo TMEM-MRI. The patients will undergo definitive breast surgery and will receive adjuvant treatments as per NCCN/ASCO guidelines. TMEM density, MenaCalc and MenaINV will be evaluated in final surgical specimen. Uth qTPERM will be correlated with TMEM density, MenaCalc and MenaINV.	Device: TMEM-MRI; TMEM MRI INFORMATION: Unilateral breast MRI will be obtained on a 3.0T whole body MRI scanner with a dedicated breast radiofrequency coil. The patient will be scanned in the prone position with an in-dwelling IV catheter for a single dose contrast agent injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tumor permeability assessed by TMEM-MRI	Tumor permeability will be assessed by TMEM-MRI, and is defined as a number of Uth units (the number of tumor voxels with permeability density above threshold divided by the number of all tumor voxels) that will be obtained from the permeability map and TMEM-MRI algorithm.	It will take you about 24 months to complete this research study outcome.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TMEM density in breast cancer patients.	TMEM density is defined as the number of TMEM units visualized by triple immunohistochemistry in 10 high power fields (40X). TMEM density will be measured with a fully automated and scalable clinical assay for identification and enumeration of TMEM utilizing digital pathology methods coupled with image analysis	It will take you about 24 months to complete this research study outcome.
MenaCalc	MenaCalc is calculated by subtracting the Z-score value of Mena11a from the Z-score value of pan-Mena, obtained by quantitative immunohistochemistry in formalin-fixed paraffin-embedded breast tumor specimens. MenaCalc can also be measured by qRT-PCR in cancer cells obtained by FNA	It will take you about 24 months to complete this research study outcome.
MenaInv	MenaInv is calculated as pixel intensity obtained by quantitative immunofluorescence per area of formalin-fixed paraffin-embedded tumor tissue. MenaINV can also be measured by qRT-PCR in cancer cells obtained by FNA	It will take you about 24 months to complete this research study outcome.

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Jesus Anampa, MD,MS, Montefiore Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2018
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: September 28, 2018
• First Submitted That Met QC Criteria: October 1, 2018
• First Posted (Actual): October 3, 2018

Study Record Updates

• Last Update Posted (Actual): July 14, 2023
• Last Update Submitted That Met QC Criteria: July 13, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: TMEM;; Magnetic resonance imaging (MRI);; breast cancer.
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms
• Other Study ID Numbers: 2018-9529

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No